ABSTRACT Among men who have sex with men (MSM), there is an urgent need to optimize the unprecedented clinical and public health benefits of pre-exposure prophylaxis (PrEP) with those who use stimulants (i.e., methamphetamine, cocaine, and crack-cocaine). Stimulant-using MSM experience substantial difficulties with navigating HIV prevention services such that this population currently accounts for one-in-ten undiagnosed HIV infections. The overarching goal of Positive Reinforcement Intervention and Sustained Motivation (PRISM) is to adapt and pilot test scalable, evidence-based motivational enhancement interventions to optimize PrEP clinical evaluation and PrEP uptake in stimulant-using MSM. PRISM will target PrEP clinical evaluation (including HIV testing) as the primary outcome, which will have a dual benefit of facilitating entry of those who are HIV- negative into the PrEP care continuum and promoting regular HIV testing in this high priority population. In Phase 1, we will collect qualitative data from members of PrEP healthcare teams (N = 10) and stimulant-using MSM who are not on PrEP (N = 30) to inform enhancements to PRISM, which includes evidence-based contingency management (CM) and motivational interviewing (MI) interventions that we have previously shown to reduce substance use and condomless anal sex in MSM. We will focus on augmenting these motivational enhancement interventions to simultaneously facilitate entry of into the PrEP care continuum. In Phase 2, we will conduct a pilot sequential multiple assignment randomized trial (SMART) with 60 HIV-negative, stimulant- using MSM with no history of PrEP use. After completing 1-week waiting period, participants will be randomized to receive: 1) a 3-month CM intervention; or 2) four sessions of MI. All participants will be assessed at three months post-randomization for non-response, defined as not having completed PrEP clinical evaluation. Using SMART methods, in a second randomization non-responders will be assigned to: 1) Switch by adding the other intervention (i.e., CM+MI or MI+CM); or 2) Continue with assessments (i.e., CM-Only or MI-Only). Findings from the pilot SMART regarding the feasibility and acceptability of the interventions, the estimated non-response rate, and cost of delivering the interventions will be reviewed with community-based providers of HIV prevention services to lay the foundation for a full-scale SMART. Consistent with the NIH OAR high priority area of ?reducing the incidence of HIV/AIDS,? this clinical research will meaningfully inform the targeted deployment of limited public health resources to optimize the unprecedented clinical and public health benefits of PrEP in stimulant-using MSM, one of highest priority populations for decreasing HIV incidence.